CD30 ligand (CD30L, CD153), the naturally occurring ligand for CD30, is a type II membrane glycoprotein that specifically binds CD30, triggering CD30 to transmit a signal via its cytoplasmic domain. CD30 and CD30L are interacting cell surface glycoproteins that are members of the TNFR and TNF superfamilies, respectively (Durkop et al, Cell, 68:421, 1992; Smith et al, Cell, 73:1349, 1993; U.S. Pat. Nos. 5,480,981; 5,677,430; 6,143,869 and 6,652,854). The expression of CD30 and CD30L is restricted to cells of the immune system and is tightly regulated. CD30 is expressed primarily on activated B cells and subsets of T cells with an activated/memory phenotype (Ellis et al., J. Immun., 151:2380, 1993; Falini et al., Blood, 85:1, 1995). CD30L is expressed at high levels on activated mouse and human T cells (Shimozato et al, Biochem. & Biophys. Res. Comm., 256:519, 1999; Armitage, J. Biological Regulators & Homeostatic Agents, 14:142, 2000). Dramatic changes in the relative gene expression of CD30L occur as B cells transit through germinal centers (Klein et al, Proc. Nat. Acad. Sci., USA, 100:2639, 2003). Thus the expression of CD30L on B cells may be stage and context specific. CD30L also appears to be a marker of a unique population of mouse dendritic cell-like accessory cells that are present in the splenic follicles where T cells interact with B cells (Kim et al., Immunity, 18:643, 2003).
Interactions between cells expressing CD30/CD30L appear to be important for the generation of strong T-cell dependent secondary or class-switched antibody responses. Evidence for such a role includes data from in vitro (Shanebeck et al., Eur. J. Immunol., 25:2147-53, 1995) and in vivo (Gaspal et al., J. Immunol., 174:3891-6, 2005) studies in mouse systems. In addition, it has been shown that in vivo treatment of mice with a blocking, but non-depleting, rat mAb to mouse CD30L inhibits the development or progression of disease in a number of models of T and/or B cell-dependent autoimmune diseases (U.S. Pat. No. 6,667,039). In models with a strong humoral immune component, inhibition of disease correlates with inhibition of the disease-associated antibody response.
Therefore it would be useful to have compositions comprising human antibodies and/or antigen binding regions that bind to CD30L for use in therapeutic and diagnostic applications